Memory dysfunction is an increased important problem among Americans, especially in those who are either aging , experiencing depression or exposed to emotional trauma. The factors contributing to memory disorder involve either a reduced or exaggerated capacity to experience arousal, which results in impaired neurotransmitter release in limbic structures that process memory. Hormones released from the adrenals after exposure to arousing events facilitate encoding and storage of memory traces by stimulating norepinephrine secretion in the brain. However, most hormones have limited capacity to enter the brain and therefore do not produce direct effects on structures that actively encode and store memory. The objective of this application is to reveal the neural pathways that arousal-related hormones utilize to affect brain regions such as the nucleus of the solitary tract (NTS), which in turn, influence norepinephrine release in limbic regions that process memory. The central hypothesis of this application proposes that regulation of memory formation by arousal- related hormones involves activation of NTS noradrenergic neurons which in turn, influence norepinephrine output in the amygdala and hippocampus. This hypothesis will be tested by 1) examining the neural pathway that mediates epinephrine's mnemonic effects on brainstem and limbic structures, 2) delineating the class of receptors in the NTS that initiate the cascade of intracellular events to increase impulse flow from this nucleus to limbic structures, and 3) by determining the neural pathways brainstem neurons utilize to influence neural activity associated with memory consolidation in both of the amygdala and hippocampus. The proposed investigations are expected to provide a better understanding of the involvement of norepinephrine in regulating memory formation and also expand current knowledge by characterizing the neural events which lead to optimal memory performance following the endogenous release of peripheral hormones. Information gained from these studies will be beneficial in identifying the underlying causes of memory disorders.